SpringerProtocols: Abstract: Genetic Analysis of Complex Traits

Genetic Analysis of Complex Traits

By: Stephen P. Bryant², Mathias N. Chiano²

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The analysis of traits and disorders that exhibit a straightforward Mendelian genetics, based on the kind of major gene models that are easy to set up in computer programs such as LINKAGE (1), has been enormously successful in facilitating identification of the genes responsible. These monogenic models typically use two alleles to represent the trait locus, one allele predisposing to development of the disease or disorder and the other allele showing a normal phenotype, with a penetrance parameter that is specified for each genotype (see Table 1). Family studies using these techniques have led to the localization of many hundreds of single gene disorders (2) and an appreciable fraction of those localized have been positionally cloned.

Table 1 Modeling the Expression of a Trait Phenotype

Parameter	Meaning
P _t	Trait allele frequency=1−Pn
f _tt	Penetrance of the t/t genotype = pT\|tt
f _tn	Penetrance of the t/n genotype = pT\|tn
f _nn	Penetrance of the n/n genotype = pT\|nn
f _t	Penetrance of the t allele = pT\|t
f _n	Penetrance of the n allele = pT\|n

Affiliation(s): (2) Gemini Research Ltd., Cambridge, UK

Book Title: Genomics Protocols

Series: Methods in Molecular Biology | Volume: 175 | Pub. Date: Jun-10-2001 | Page Range: 11-27 | DOI: 10.1385/1-59259-235-X:011

Subject: Genetics/Genomics

References

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1.	Lathrop, G. M. and Lalouel, J. M. (1984) Easy calculations of lod scores and genetic risks on small computers. Am. J. Hum. Genet. 36, 460–465.

2.	McKusick, V. A. (1994) Mendelian Inheritance in Man, in Catalogs of Human Genes and Genetic Disorders, 11th ed., John Hopkins University Press, Baltimore, MD.

3.	Bryant, S. P. (1994) Genetic linkage analysis, in Guide to Human Genome Computing (Bishop, M. J. B., ed.), Academic Press, London, pp. 59–110.

4.	Bryant, S. P. (1998) Constructing and using genetic maps, in Handbook of Genome Analysis (Spurr, N. K., Young, B. D., and Bryant, S. P., eds.), ICRF Blackwells, Oxford, UK, pp. 43–87.

5.	Grant, S. F. A., Reid, D. M., Blake, G., Herd, R., Fogelman, I., and Ralston, S. H. (1996) Reduced bone density and osteoporosis associated with a polymorphic Spl binding site in the collagen type I-alpha 1 gene. Nature Genet. 14, 203–305.

6.	Masi, L., Becherini, L., Gennari, L., Colli, E., Mansani, R., Falchetti, A., et al. (1998) Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women. Biochem. Biophys. Res. Commun. 245, 622–626.

7.	Kruglyak, L. and Lander, E. S. (1995) Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am. J. Hum. Genet. 57, 439–454.

8.	Kruglyak, L. and Lander, E. S. (1995) High-resolution genetic mapping of complex traits. Am. J. Hum. Genet. 56, 1212–1223.

9.	Kruglyak, L., Daly, M. J., Reeve-Daly, M. P., and Lander, E. S. (1996) Parametric and nonparametric linkage analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363.

10.	Holman, P. and Clayton, D. (1995) Efficiency of typing unaffected relatives in an affected-sib-pair linkage study with single-locus and multiple tightly linked markers. Am. J. Hum. Genet. 57, 1221–1232.

11.	Risch, N. (1990a) Linkage strategies for genetically complex traits: I. multilocus models. Am. J. Hum. Genet. 46, 222–228.

12.	Risch, N. (1990b) Linkage strategies for genetically complex traits: II. The power of affected relative pairs. Am. J. Hum. Genet. 46, 229–241.

13.	Holmans, P. (1993) Asymptotic properties of affected-sib-pair linkage analysis. Am. J. Hum. Genet. 52, 362–374.

14.	Lange, K. (1986a) A test statistic for the affected-sib-set method. Ann. Hum. Genet. 50, 283–290.

15.	Weeks, D. E. and Lange, K. (1988) The affected-pedigree-member method of linkage analysis. Am. J. Hum. Genet. 42, 315–326.

16.	Babron, M. C., Martinez, M., Bonaite-Pellie, C., and Clerget-Darpoux, F. (1993) Linkage detection by the affected-pedigree-member method: what is really tested? Genet. Epidemiol. 10, 389–394.

17.	Allison, D. B., Thiel, B., St Jean, P., Elston, R. C., Infante, M. C., and Schork, N. J. (1998) Multiple phenotype modelling in gene-mapping studies of quantitative traits: power advantages. Am. J. Hum. Genet. 63, 1190–1201.

18.	Haseman, J. K. and Elston, R. C. (1972) The investigation of linkage between a quantitative trait and a marker locus. Behav. Genet. 2, 3–19.

19.	Fulker, D. W. and Cardon, L. R. (1994) A sib-pair approach to interval mapping of quantitative trait loci. Am. J. Hum. Genet. 54, 1092–1103.

20.	Searle, S. R., Casella, G., and McCulloch, C. E. (1992) Variance Components, John Wiley and Sons, New York.

21.	Schork, N. J., North, S. P., Lindpainter, K., and Jacob, H. J. (1996) Extensions to quantitative trait locus mapping in experimental organisms. Hypertension 28, 1104–1111.

22.	Amos, C. I. (1994) Robust variance-component approach for assessing genetic linkage pedigrees. Am. J. Hum. Genet. 54, 535–543.

23.	Goldgar, D. E. (1990) Multipoint analysis of human quantitative genetic variation. Am. J. Hum. Genet. 47, 957–967.

24.	Schork, N. J. (1993) Extended multipoint identity-by-descent analysis of human quantitative traits: efficiency, power and modelling considerations. Am. J. Hum. Genet. 53, 1306–1319.

25.	SAGE (1994) Statistical Analysis for Genetic Epidemiology, Computer package, available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH.

26.	GAS Package Version 2.0, available from Dr. Alan Young, Oxford University (http://users.ox.ac.uk/~ayoung/gas.html).

27.	Blanjero, J. (1996) SOLAR: Sequential Oligogenic Linkage Analysis Routines, Population Genetics Lab Technical Report No. 6, Southwest Foundation for Biomedical Research, San Antonio, TX.

28.	Neale, M. C. (1997) Mx: Statistical Modelling, 2nd ed., Box 980126 WCV, Richmond, VA 23298.

29.	Chiano, M. N. and Clayton, D. G. (1998) Genotype relative risks under ordered restriction. Genet. Epidemiol. 15, 135–146.

30.	Zeger, S. L. and Liang, K. Y. (1986) Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42, 121–130.

31.	Tregouet, D. A., Ducimetiere, P., and Tiret, L. (1997) Testing association in candidate-genes, markers and phenotype in related individuals, by use of estimating equations. Am. J. Hum. Genet. 61, 189–199.

32.	Excoffier, L. and Slatkin, M. (1995) Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol. Biol. Evol. 12, 921–927.

33.	Chiano, M. N. and Clayton, D. G. (1998) Fine genetic mapping using haplotype analysis and the missing data problem. Ann. Hum. Genet. 62, 55–60.

34.	Martin, R. B., Maclean, C. J., Sham, P. C., Straub, R. E., and Kendler, K. S. (2000) The trimmed-haplotype test for linkage disequilibrium. Am. J. Hum. Genet. 66, 1062–1075.

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